The present invention relates to treating blood vessels, and in particular, to preventing restenosis after an angioplasty dilatation treatment, or other controlled injury, of a stenotic region of a blood vessel.
Percutaneous transluminal coronary angioplasty (PTCA) is commonly used to treat an artery obstructed by a stenosis. In PTCA, a catheter having a balloon at its distal end is advanced through the cardiovascular system until the balloon lies across the stenosis. The balloon is then inflated under a pressure and for a time sufficient to cause the blood vessel to be permanently dilated in region of the stenosis. This permanent dilation results from the force of the balloon breaking an internal elastic laminate boundary between an intima and a medial cell layer of the blood vessel. This permanent dilation caused by PTCA is a controlled injury having beneficial therapeutic effects. Other therapeutic injuries can be caused by interventional procedures other than PTCA.
The blood vessel frequently reacts to the disruption of these tissue layers (caused by PTCA or other intervention) by restenosing, sometimes resulting in reocclusion of the blood vessel. A significant factor in restenosis is the proliferation of smooth muscle cells in the medial cell layer of the blood vessel. Another factor in restenosis includes an acute thrombotic reaction which is associated with exposure of the medial cell layer to blood circulating in the vessel. Finally, elastic recoil in the blood vessel wall, which reduces or eliminates the permanency of the dilation, and remodeling of plaque in the stenosed region are also associated with restenosis.
Various attempts at solving the problem of restenosis after PTCA, or other vessel injuries, have been offered but none provide an overall acceptable solution. These prior attempts include using drugs to inhibit medial smooth cell proliferation or the delivery of ionizing radiation (e.g., Beta emitters, x-rays, gamma-rays) to neutralize the medial smooth cell layer and thereby prevent smooth cell proliferation. However, delivery of ionizing radiation is difficult to handle and poses a risk of exposure to health care providers. Various methods of applying heat to the vessel wall (e.g., conductive transfer via hot balloon, laser, infrared) have been presented to minimize restenosis. Examples of several of these approaches are disclosed in Weinberger U.S. Pat. No. 5,503,613, Abele et al. U.S. Pat. No. 5,496,311, Sterzer U.S. Pat. Nos. 4,924,863 and 5,098,429, Lennox U.S. Pat. No. 4,955,377, and Spears U.S. Pat. No. 5,092,841. However, none of these methods satisfactorily prevent restenosis after a PTCA treatment or other blood vessel injury. Although stents have also been used to open and maintain a blood vessel in a patent state, stents require permanent placement in the vessel.